Mutants of Streptococcus mutans and wild type strains from which they were derived will be used to characterize the course of synthesis of soluble and insoluble glucans by extracellular, cell-associated, and affinity chromatography-purified glucosyl transferases. Additionally, the glucan polymers formed by the wild type in vivo in two rat caries models will be compared with in vitro synthesized glucans. Specifically, the temporal formation of glucan types, the changes in linkages and branches, and increases in molecular size will be followed by gas-liquid and gel chromatography to address such question as (1) how do the multiple synthetic and hydrolytic enzymes act together to form adhesive plaques, (2) what are the enzymatic natures of the defects in our mutants of diminished virulence, (3) what is the role of endogenous glucanase in polymer formation, and (4) do the polymers formed in vivo in the rodent host reflect those formed in vitro? Also, using mutants competent in plaque formation but of diminished virulence and other non-virulent plaque formers, animal studies will be conducted to (1) demonstrate protection against virulent wild type infection via pre-emptive infection with a non-virulent strain, as well as (2) the displacement of virulent wild type by exposure of rats to excess non-virulent cells. In such experiments we will employ strains which, although persistent in the oral cavity and able to form plaque, are notably less virulent than S. mutans wild type. The possible role of immunological protection will be assessed in animals exposed to the non-virulent plaque formers via gastric intubation. In a final component of the study, a mutant defective in adsorption to hydroxyapatite will be sought by an enrichment procedure, inasmuch as sorption is the assumed first step in adhesive plaque formation. The virulence of this adsorption-defective mutant(s) will be assessed with respect to its wild type progenitor.